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Background Tenecteplase (TNK) is increasingly used for thrombolysis in large vessel occlusion (LVO) stroke and may promote early recanalization prior to endovascular thrombectomy (EVT). Emerging data suggest that thrombus dynamics, including migration and fragmentation, may influence angiographic findings and EVT triage. Real-world predictors of early recanalization in transferred patients remain incompletely defined.Methods We performed a retrospective cohort study of consecutive patients with LVO stroke who received TNK at outside hospitals and were transferred to a comprehensive stroke center (2023–2025).Of 99 TNK-treated LVO patients, 82 met inclusion criteria for EVT evaluation. The remaining patients were excluded due to incomplete data or ineligibility for EVT based on clinical or imaging criteria (e.g., large infarct core or poor baseline status).Early recanalization was defined as (1) clinical and/or imaging improvement obviating EVT or (2) complete recanalization on initial angiography prior to intervention. Early neurological improvement was defined as a reduction in NIHSS score following TNK administration prior to EVT evaluation.Clinical, imaging, and treatment variables were analyzed using univariate comparisons.Results Ninety-nine TNK-treated patients with LVO were screened, of whom 82 met criteria for the primary analysis. Spontaneous recanalization occurred in 20.7% (17/82), while 79.3% (65/82) of patients without early recanalization underwent EVT.In exploratory analysis of the structured subset, baseline stroke severity was similar between groups (median NIHSS 15 vs 16), while post-treatment NIHSS favored the spontaneous recanalization group (median 6 vs 14), reflecting greater early neurological improvement.Recanalization was strongly associated with occlusion location, with higher rates observed in distal occlusions (M2+) compared to proximal LVO (ICA/M1), supporting an anatomic and thrombus-related influence on TNK response (p<0.05, exploratory).Safety outcomes were favorable: no symptomatic intracranial hemorrhage occurred in the spontaneous recanalization group (0/17) compared with 6.15% (4/65) in patients without early recanalization. Mortality or transition to comfort measures was similar between groups (17.6% vs 15.4%).Conclusions In this real-world cohort of transferred LVO stroke patients, approximately one in five patients demonstrated early recanalization after TNK. Recanalization appears primarily driven by occlusion location and thrombus characteristics rather than baseline stroke severity, with no increase in hemorrhagic complications. These findings support the role of TNK in promoting early reperfusion and highlight the importance of thrombus dynamics in EVT triage decisions.Disclosures C. Amankwah: None. R. Miller: None. A. Adcock: None.Abstract E-289 Figure 1Recanalization rate by occlusion location following tenecteplase administration. Spontaneous recanalization occurred more frequently in distal occlusions (M2+) compared with proximal occlusions (ICA/M1). The ‘Other’ category includes posterior circulation occlusions (e.g., basilar, PCA) and less common or mixed occlusion sites. This distribution highlights a strong association between occlusion location and likelihood of early recanalizationAbstract E-289 Figure 2Early neurological improvement following tenecteplase administration. Patients with spontaneous recanalization demonstrated greater early neurological improvement compared to those without early recanalization (median NIHSS improvement 5 vs 2), consistent with early reperfusion and treatment response